Automatic pipette machines or robots are used in the chemical and biological fields to automatically pipette fluids from one place to another, without the need for direct human involvement. Generally, automated pipette robots have three axes of motion to allow a moveable tip head to access different containers with fluid samples in a given area. One class of robots are known as θ-z-θ robots which combine rotational (θ) and vertical (z) motion of a robot arm holding the tip head with rotational (θ) motion of a carousel that holds the samples, thereby allowing the tip head to access the samples on the carousel. A more common class of robots are x-y-z gantry style robots (e.g. BioMek FX™, Qiagen™ Biorobots™) where the moveable tip head moves along one vertical axis and two orthogonal horizontal axes of motion. To avoid contamination, many automatic pipette machines use disposable pipette tips. Typically, the tip head on these robots has one or more nozzles that receive a pipette tip.
Typically, the tip heads on the automated pipette robots can accommodate only one size of disposable pipette tip. However, a given size of pipette tip is best suited for pipetting a limited range of volumes of fluid. Some processes require that a wider range of volumes of fluid be transferred from one place to another than can be accommodated by the tip. In such instances, either the pipette head must make multiple trips between the source and destination locations in order to cumulatively transfer the required volume, or human intervention is required to transfer the volumes that cannot be effectively handled by the pipette machine. It would be desirable to provide an automated pipette machine capable of pipetting a wider range of volumes.
Automated pipette systems often use a hydraulic fluid in the fluid lines that connect the pump to the pipette tip head because hydraulic fluids are less compressible than air. As the liquid volume in the pipette tip increases, the pressure drop between the pump and the tip head increases. It is easier to calibrate the pump to attain the desired pipette volume accuracy if most of the volume in the line between the pump and the tip head is a hydraulic fluid. In addition, for positive displacement pumps, the volume of liquid the pump can draw into the tip with a single piston stroke is higher using a hydraulic fluid.
Existing automated pipette technology is limited to aspirating a maximum of approximately 1 mL of liquid. In these machines, there is tubing of a relatively small diameter and of sufficient length between the tip head and the pump to accommodate up to 1 mL of air displaced from the pipette tip during aspiration. Small diameter tubing is used so that if there is an interface between hydraulic fluid and air in a section of the tubing that is not horizontal, the hydraulic fluid does not flow down into the air volume. If this occurs, then air can be inadvertently introduced into the pump, causing a loss of volumetric dispensing accuracy. Many analysis processes require that volumes significantly greater than 1 mL be pipetted. To pipette larger volumes of fluid a longer tube can be used while maintaining the diameter of the tube constant so that the tube remains small enough in cross-section so that no air is inadvertently introduced into the pump during operation.
A longer tube, however, has several drawbacks associated with it. For example, in a long length of tubing there is an increased chance that as the hydraulic fluid is drawn into the pump, there will be breaks at the air-hydraulic fluid interface resulting in the formation of discrete bubbles between the main interface and the nozzle. When the pump initiates the dispensing step, these bubbles will be ahead of the main interface and may be expelled from the nozzle, contaminating the tip and potentially contaminating the fluid that the tip aspirated, and the fluid volume into which the tip is dispensing. Additionally, a long length of tubing provides increased pressure drop at a given fluid flow-rate, which in turn, means that pump cavitation would occur at a relatively lower flow-rate during aspiration. Furthermore, the increased pressure drop reduces the maximum dispensing flow-rate. Another drawback is that, for both the aspirating and dispensing steps, the higher pressure drop through a long length of tubing may increase the chance of leakage at connections between the different tubes, the pump, and the nozzle, since higher (or lower) initial pressures are required at the pump to achieve operation.
These drawbacks associated with longer tubing as described above also apply to the use of small diameter tubing for 1 ml machines that are currently in use. In other words, for any machine that incorporates a length of relatively small diameter tubing which functions as a reservoir for air during operation, the above described problems are present.
It would be desirable to have a system that can transfer volumes of fluid without incorporating long hydraulic fluid lines.
Another drawback related to current automated pipette machines relates to the disposal of used pipette tips. There are currently various mechanisms proposed and in use for removing disposable pipette tips from the pipette nozzle. However, many of these mechanisms are relatively intricate, thereby increasing the complexity of the pipette machines and the cost of manufacture. Furthermore, many of the devices of the prior art eject the pipette tip in an uncontrolled manner, usually into a disposal bin, thereby making it impractical to reuse the tip if desired. For example, in some analysis techniques, the same material is transferred in non-consecutive steps, in which case reuse of the tip is desirable since contamination is not an issue. It would be desirable to have a pipette machine that is capable of reusing a pipette tip.